Mitochondrial DNA Mutation Rates

Mitochondrial DNA Mutation Rates

David A. Plaisted


Recently an attempt was made to estimate the age of the human race using mitochondrial DNA. This material is inherited always from mother to children only. By measuring the difference in mitochondrial DNA among many individuals, the age of the common maternal ancestor of humanity was estimated at about 200,000 years.

A problem is that rates of mutation are not known by direct measurement, and are often computed based on assumed evolutionary time scales. Thus all of these age estimates could be greatly in error. In fact, many different rates of mutation are quoted by different biologists.

It shouldn't be very hard explicitly to measure the rate of mutation of mitochondrial DNA to get a better estimate on this age. From royal lineages, for example, one could find two individuals whose most recent common maternal ancestor was, say, 1000 years ago. One could then measure the differences in the mitochondrial DNA of these individuals to bound its mutation rate. This scheme is attractive because it does not depend on radiometric dating or other assumptions about evolution or mutation rates. It is possible that in 1000 years there would be too little difference to measure. At least this would still give us some useful information.

(A project for creation scientists!)

Along this line, some work has recently been done to measure explictly the rate of substitution in mitochondrial DNA. The reference is Parsons, Thomas J., et al., A high observed substitution rate in the human mitochondrial DNA control region, Nature Genetics vol. 15, April 1997, pp. 363-367. The summary follows:

"The rate and pattern of sequence substitutions in the mitochondrial DNA (mtDNA) control region (CR) is of central importance to studies of human evolution and to forensic identity testing. Here, we report a direct measurement of the intergenerational substitution rate in the human CR. We compared DNA sequences of two CR hypervariable segments from close maternal relatives, from 134 independent mtDNA lineages spanning 327 generational events. Ten subsitutions were observed, resulting in an empirical rate of 1/33 generations, or 2.5/site/Myr. This is roughly twenty-fold higher than estimates derived from phylogenetic analyses. This disparity cannot be accounted for simply by substitutions at mutational hot spots, suggesting additional factors that produce the discrepancy between very near-term and long-term apparent rates of sequence divergence. The data also indicate that extremely rapid segregation of CR sequence variants between generations is common in humans, with a very small mtDNA bottleneck. These results have implications for forensic applications and studies of human evolution." (op. cit. p. 363).

The article also contains this section:

"The observed substitution rate reported here is very high compared to rates inferred from evolutionary studies. A wide range of CR substitution rates have been derived from phylogenetic studies, spanning roughly 0.025-0.26/site/Myr, including confidence intervals. A study yielding one of the faster estimates gave the substitution rate of the CR hypervariable regions as 0.118 +- 0.031/site/Myr. Assuming a generation time of 20 years, this corresponds to ~1/600 generations and an age for the mtDNA MRCA of 133,000 y.a. Thus, our observation of the substitution rate, 2.5/site/Myr, is roughly 20-fold higher than would be predicted from phylogenetic analyses. Using our empirical rate to calibrate the mtDNA molecular clock would result in an age of the mtDNA MRCA of only ~6,500 y.a., clearly incompatible with the known age of modern humans. Even acknowledging that the MRCA of mtDNA may be younger than the MRCA of modern humans, it remains implausible to explain the known geographic distribution of mtDNA sequence variation by human migration that occurred only in the last ~6,500 years.

One biologist explained the young age estimate by assuming essentially that 19/20 of the mutations in this control region are slightly harmful and eventually will be eliminated from the population. This seems unlikely, because this region tends to vary a lot and therefore probably has little function. In addition, the selective disadvantage of these 19/20 of the mutations would have to be about 1/300 or higher in order to avoid producing more of a divergence in sequences than observed in longer than 6000 years. This means that one in 300 individuals would have to die from having mutations in this region. This seems like a high figure for a region that appears to be largely without function. It is interesting that this same biologist feels that 9/10 of the mutations to coding regions of DNA are neutral. This makes the coding regions of DNA less constrained than the apparently functionless control region of the mitochondrial DNA!

Another discussion of mitochondrial DNA mutation rates and their implications may be found at

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